Otitis externa, involving the ear canal portion of the external ear, is a common otologic problem occurring mainly during hot, humid weather, and five times more frequently in swimmers than in nonswimmers. In the incipient stage, symptoms include itching and pain in the ear canal, and tenderness when pressure is applied around the external auditory meatus, the ear lobe is pulled or the jaw is moved. In the definitive stage, suppuration occurs in the ear canal and hearing may be decreased. Over 90% of cases of otitis externa are due to bacterial and fungal infections. Treatment with topical agents is common, including antibacterial and/or antifungal creams and drops. Oral antibiotics may be used if cellulitis symptoms are present.
Otitis media, a term used to describe infections of the middle ear, is also very common. A relatively high percentage of the population, both adults and particularly children, are affected. It has been estimated that nearly 95% of all children experience one or more episodes of otitis by age 9, and that about 15% of all visits by children to pediatricians are in regard to otitis media. In children, the disease is most often associated with upper respiratory afflictions which trigger a transudate secretion response in the Eustachian tube and middle ear. Bacteria and viruses migrate from the naso-pharynx to the middle ear via the Eustachian tube, and can cause the Eustachian tube to become blocked, preventing ventilation and drainage of the middle ear.
In its more severe forms, purulent exudate, toxins and endogenous anti-microbial enzymes are formed in the middle ear, which can cause irreparable damage to sensory-neural and sound conducting structures. It has been reported that sensory-neural hearing loss occurred in 35.8 percent of children with otitis media with effusion. It is estimated that over one billion dollars are spent annually in the United States on the treatment and prevention of otitis media.
Current methods of treatment generally involve the systemic use of antibiotics; the use of ear drops (which have not been approved by the Food and Drug Administration); and in more chronic cases, the insertion of a myringotomy tube through an incision in the eardrum to allow ventilation and drainage of the middle ear cavity. Systemic administration of antibiotics generally requires high initial doses and an appreciable time lag to achieve therapeutic levels in the middle ear. With respect to currently known ear drops, there has been growing concern recently that medications in the middle ear cavity as well as inflammatory and infectious substances can cause inner ear damage. It is generally believed that damaging substances in the middle ear space can gain access into the inner ear across the round window membrane, which has been demonstrated to be semipermeable. Hearing loss is believed a result of impairment, damage or destruction of inner ear cochlear hair cells.
Ciprofloxacin and its preparation is described in U.S. Pat. No. 4,670,444, which is hereby incorporated by reference. Studies have shown the usefulness of local ciprofloxacin in ear infections. A study of the clinical and bacteriological efficacy of ciprofloxacin in human patients affected by chronic otitis media in the acute stage is reported in "Topical and Oral Treatment of Chronic Otitis Media With Ciprofloxacin" by Esposito, D'Errico and Montanaro in Arch. Otolaryngo Head Neck Surg., Vol 116, May 1990, p.556-559. Three drops of ciprofloxacin in saline solution were administered twice a day in affected ears for 5 to 10 days. A high percentage of favorable clinical response and bacteriological eradication was observed without ototoxicity.
A study entitled "Local Therapy for Pseudomonas Infections of the Ear" by G. Stang in Laryngol Rhino Otol. 68 (12): 653-656 (1989) reports that infections of the middle and external ear in humans caused by Pseudononas aeruginosa can be cured by local therapy with ciprofloxacin and tutofusin very quickly and without any complications. Function disturbance of the middle and internal ear cleared up and the functions returned to normal.
A study of the "Efficacy of 2 Regimens of Local Ciprofloxacin in the Treatment of Ear Infections" by Garcia-Rodriguez et al was reported in Preprint: Drugs 45 (Suppl.) 1993, pages 40-41. Ear infections of several types were treated with 3 drops per 8 hours for 7 days with 0.5% ciprofloxacin solution and in another group of patients with 0.3% ciprofloxacin solution. The results obtained showed that local ciprofloxacin is an effective treatment for ear infections with few and mild side effects and without ototoxicity.
While ciprofloxacin-containing ear drops have been prepared and administered in studies, currently, there is no ciprofloxacin or other antibiotic preparation approved for topical middle ear use, and which can be prescribed for a patient. What is needed is a non-irritating, non-sensitizing, non-ototoxic composition which can be readily used by a patient for topical treatment of otitis, particularly otitis media, and most particularly, otorrhea.